Direct Cyclopalladation of Fluorinated Benzyl Amines by Pd3(OAc)6: The Coexistence of Multinuclear Pdn Reaction Pathways Highlights the Importance of Pd Speciation in C–H Bond Activation
Abstract
Palladacycles are key intermediates in catalytic C-H bond functionalization reactions and important precatalysts for cross-couplings.It is commonly believed that palladacycle formation occurs throughthe reaction of a substrate bearing a C-H bond ortho to a suitable metal-directing group for interaction with, typically,mononuclear "Pd(OAc)(2)" species, with cyclopalladationliberating acetic acid as the side product. In this study, we showthat N,N-dimethyl-fluoro-benzylamines, which can be cyclopalladated either ortho or para to fluorine affording two regioisomericproducts, can occur by a direct reaction of Pd3(OAc)(6), proceeding via higher-order cyclopalladated intermediates.Regioselectivity is altered subtly depending on the ratio of substrate:Pd3(OAc)(6) and the solvent used.
Our findings are importantwhen considering mechanisms of Pd-mediated reactions involving theintermediacy of palladacycles, of particular relevance in catalyticC-H bond functionalization chemistry.